This project focuses on the late complications of therapy for cancer in childhood or adolescence. Mortality and morbidity, especially second cancers and fertility of long-term survivors of childhood and adolescent cancer, are studied for information on the carcinogenicity, gonadal toxicity, and possible mutagenicity of cancer treatment, to uncover hereditary patterns of cancer, and to delineate the factors that predispose to second cancers. Current phases include the field work (interviews) for a study of survival after childhood leukemia, analysis of data collected from interviews with 2300 survivors of childhood and adolescent cancer and 3500 of their siblings as controls to learn about their subsequent health and fertility, and the health of their offspring; and planning for an imaging study of women who were treated for Wilms' tumor. From our large study of long-term cancer survivors, we found that menopause occurred earlier in survivors, especially after treatment with radiation below the diaphragm and alkylating agents. Also, we reported that smoking rates were only slightly less in survivors, although there is a trend for less smoking among survivors diagnosed more recently. These studies have been expanded into new areas. Plans are underway to recontact the remaining survivors of our cohort of long-term survivors of childhood cancer to evaluate their risk of second cancers and health problems, and to expand our studies of cancer and birth defects in the offspring of survivors. This study will consist of an interview and blood specimens for studies of cancer susceptibility. Plans to include blood specimens from our cohort of leukemia survivors are being developed.